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Genome wide screen

Tamara Zoranovic, Jan Manent, Lee Willoughby, Ricardo Matos de Simoes, John E La Marca, Sofya Golenkina, Xia Cuiping, Susanne Gruber, Belinda Angjeli, Elisabeth Eva Kanitz, Shane J F Cronin, G Gregory Neely, Andreas Wernitznig, Patrick O Humbert, Kaylene J Simpson, Constantine S Mitsiades, Helena E Richardson, Josef M Penninger
Oncogenic mutations in the small GTPase Ras contribute to ~30% of human cancers. However, Ras mutations alone are insufficient for tumorigenesis, therefore it is paramount to identify cooperating cancer-relevant signaling pathways. We devised an in vivo near genome-wide, functional screen in Drosophila and discovered multiple novel, evolutionarily-conserved pathways controlling Ras-driven epithelial tumorigenesis. Human gene orthologs of the fly hits were significantly downregulated in thousands of primary tumors, revealing novel prognostic markers for human epithelial tumors...
October 16, 2018: PLoS Genetics
Michael Aregger, Megha Chandrashekhar, Amy Hin Yan Tong, Katherine Chan, Jason Moffat
CRISPR-Cas9 technology provides a simple way to introduce targeted mutations into mammalian cells to induce loss-of-function phenotypes. The CRISPR-Cas9 system has now successfully been applied for genetic screens in many cell types, providing a powerful tool for functional genomics with manifold applications. Genome-wide guide-RNA (gRNA) libraries allow facile generation of a pool of cells, each harboring a gene knockout mutation that can be used for the study of gene function, pathway analysis or the identification of genes required for cellular fitness...
2019: Methods in Molecular Biology
Karyna Rosario, Kaitlin A Mettel, Bayleigh E Benner, Ryan Johnson, Catherine Scott, Sohath Z Yusseff-Vanegas, Christopher C M Baker, Deby L Cassill, Caroline Storer, Arvind Varsani, Mya Breitbart
Viruses encoding a replication-associated protein (Rep) within a covalently closed, single-stranded (ss)DNA genome are among the smallest viruses known to infect eukaryotic organisms, including economically valuable agricultural crops and livestock. Although circular Rep-encoding ssDNA (CRESS DNA) viruses are a widespread group for which our knowledge is rapidly expanding, biased sampling toward vertebrates and land plants has limited our understanding of their diversity and evolution. Here, we screened terrestrial arthropods for CRESS DNA viruses and report the identification of 44 viral genomes and replicons associated with specimens representing all three major terrestrial arthropod lineages, namely Euchelicerata (spiders), Hexapoda (insects), and Myriapoda (millipedes)...
2018: PeerJ
Joo-Yeon Lee, Jisun Kim, Sung-Won Kim, Sue K Park, Sei Hyun Ahn, Min Hyuk Lee, Young Jin Suh, Dong-Young Noh, Byung Ho Son, Young Up Cho, Sae Byul Lee, Jong Won Lee, John L Hopper, Joohon Sung
"BRCAX" refers breast cancers occurring in women with a family history predictive of being a BRCA1/2 mutation carrier, but BRCA1/2 genetic screening has failed to find causal mutations. In this study, we report the findings of the genetic architecture of BRCAX with novel and redefined candidate loci and their potential impacts on preventive strategy. We performed a genome-wide association study involving 1,469 BRCAX cases from the Korean Hereditary Breast Cancer study, and high-risk breast cancer cases (1,482 Asians and 9,902 Europeans) from the Breast Cancer Association Consortium...
October 15, 2018: Scientific Reports
Valentina D'ambrosio, Antonia Squarcella, Flaminia Vena, Daniele Di Mascio, Sara Corno, Cristina Pajno, Maria Grazia Piccioni, Roberto Brunelli, Antonio Pizzuti, Pierluigi Benedetti Panici, Antonella Giancotti
Non-invasive prenatal test (NIPT) has revolutionized the approach to prenatal diagnosis and, to date, it is the most superior screening method for the common autosomal aneuploidies, mostly trisomy 21. This screening has having a significant population-wide impact on the uptake of conventional screening and diagnostic testing. In recent years, emerging genomic technologies, largely based around next generation sequencing, have expanded the analyses to the sub- chromosomal aneuploidies, however, further clinical validation studies are needed to better characterize this technology...
October 11, 2018: Minerva Ginecologica
Meng Cai, Sitao Li, Yunfei Shuai, Jie Li, Jieqiong Tan, Qiyi Zeng
Tumor necrosis factor α (TNF-α), a pivotal cytokine in sepsis, protects the host against pathogens by promoting an inflammatory response while simultaneously inducing apoptosis of the vascular endothelium. Unfortunately, inhibitors targeting certain components of the TNF-α signaling pathway to reduce cellular apoptosis have failed to translate into clinical applications, partly due to the adverse effects of excessive immunosuppression. In an attempt to discover potential targets in the TNF-α signaling pathway to modulate moderate inflammation and apoptosis during the development of sepsis, we performed a pooled genome-wide CRISPR/Cas9 knockout screen in human umbilical vein endothelial cells (HUVECs)...
October 14, 2018: Journal of Cellular Physiology
Peter E Burby, Zackary W Simmons, Lyle A Simmons
Bacteria coordinate DNA replication and cell division, ensuring a complete set of genetic material is passed onto the next generation. When bacteria encounter DNA damage, a cell cycle checkpoint is activated by expressing a cell division inhibitor. The prevailing model is that activation of the DNA damage response and protease mediated degradation of the inhibitor is sufficient to regulate the checkpoint process. Our recent genome-wide screens identified the gene ddcA as critical for surviving exposure to DNA damage...
October 13, 2018: Molecular Microbiology
Bhairab N Singh, Naoko Koyano-Nakagawa, Wuming Gong, Ivan P Moskowitz, Cyprian V Weaver, Elizabeth Braunlin, Satyabrata Das, Jop H van Berlo, Mary G Garry, Daniel J Garry
The mammalian heart has a limited regenerative capacity and typically progresses to heart failure following injury. Here, we defined a hedgehog (HH)-Gli1-Mycn network for cardiomyocyte proliferation and heart regeneration from amphibians to mammals. Using a genome-wide screen, we verified that HH signaling was essential for heart regeneration in the injured newt. Next, pharmacological and genetic loss- and gain-of-function of HH signaling demonstrated the essential requirement for HH signaling in the neonatal, adolescent, and adult mouse heart regeneration, and in the proliferation of hiPSC-derived cardiomyocytes...
October 12, 2018: Nature Communications
Vahid Hasanvand, Mehdi Kamali, Jahangir Heydarnejad, Hossain Massumi, Anders Kvarnheden, Arvind Varsani
Turncurtoviruses (family: Geminiviridae; genus: Turncurtovirus) appear to have a high degree of genetic variation in Iran. Leafhoppers of the species Circulifer haematoceps (Mulsant and Rey, 1855) (family: Cicadellidae) were collected in 2014 from three geographical regions in south-eastern Iran (Orzoeyeh, Jiroft and Sirjan; Kerman province) and screened for the presence of turncurtoviruses using a combination of PCR and rolling circle amplification (RCA) methods. Eleven genomes of turncurtovirus were recovered and sequenced...
October 11, 2018: Virus Genes
Michael Inouye, Gad Abraham, Christopher P Nelson, Angela M Wood, Michael J Sweeting, Frank Dudbridge, Florence Y Lai, Stephen Kaptoge, Marta Brozynska, Tingting Wang, Shu Ye, Thomas R Webb, Martin K Rutter, Ioanna Tzoulaki, Riyaz S Patel, Ruth J F Loos, Bernard Keavney, Harry Hemingway, John Thompson, Hugh Watkins, Panos Deloukas, Emanuele Di Angelantonio, Adam S Butterworth, John Danesh, Nilesh J Samani
BACKGROUND: Coronary artery disease (CAD) has substantial heritability and a polygenic architecture. However, the potential of genomic risk scores to help predict CAD outcomes has not been evaluated comprehensively, because available studies have involved limited genomic scope and limited sample sizes. OBJECTIVES: This study sought to construct a genomic risk score for CAD and to estimate its potential as a screening tool for primary prevention. METHODS: Using a meta-analytic approach to combine large-scale, genome-wide, and targeted genetic association data, we developed a new genomic risk score for CAD (metaGRS) consisting of 1...
October 16, 2018: Journal of the American College of Cardiology
Robert C Orchard, Meagan E Sullender, Bria F Dunlap, Dale R Balce, John G Doench, Herbert W Virgin
Noroviruses (NoVs) are a leading cause of gastroenteritis world-wide, yet host factors that restrict NoV replication are not well understood. Here, we use a CRISPR activation (CRISPRa) genome-wide screening to identify host genes that can inhibit murine norovirus (MNoV) replication in human cells. Our screens identified with high confidence 49 genes that can inhibit MNoV infection when overexpressed. A significant number of these genes are in interferon and immune regulation signaling networks, but surprising, the majority of the genes identified are not associated with innate or adaptive immunity nor with any antiviral activity...
October 10, 2018: Journal of Virology
Bo-Wei Han, Hua Ye, Pan-Pan Wei, Bo He, Cai Han, Zhen-Hua Chen, Yue-Qin Chen, Wen-Tao Wang
BACKGROUND: Long noncoding RNAs (lncRNAs) are known to play important roles in different cell contexts, including cancers. However, little is known about lncRNAs in cholangiocarcinoma (CCA), a cholangiocyte malignancy with poor prognosis, and associated with chronic inflammation and damage to the biliary epithelium. This study determined whether lncRNAs were dysregulated and participated in disease diagnosis or pivotal inflammation pathways through a genome-wide lncRNA screening and functional analysis...
October 11, 2018: BMC Genomics
Petr Šmarda, Lucie Horová, Ondřej Knápek, Heidi Dieck, Martin Dieck, Katarína Ražná, Pavel Hrubík, Laszlo Orlóci, Laszlo Papp, Kristýna Veselá, Pavel Veselý, Petr Bureš
Ginkgo biloba , the last extant representative of a lineage of Mesozoic gymnosperms, is one of the few seed plants with an exceptionally long (~300 Myr) evolutionary history free of genome-wide duplications (polyploidy). Despite this genome conservatism, we have recently found a viable spontaneous tetraploid Ginkgo sapling during routine screening of several plants, demonstrating that natural polyploidy is possible in Ginkgo . Here we provide a much wider flow cytometry survey of ploidy in some European Ginkgo collections, and own seedlings (>2200 individuals and ~200 cultivars)...
2018: Horticulture Research
Jason P Lynch, Cammie F Lesser
Several genome-wide screens have been conducted to identify host cell factors involved in the pathogenesis of bacterial pathogens whose virulence is dependent on type III secretion systems (T3SSs), nanomachines responsible for the translocation of proteins into host cells. In the most recent of these, Pacheco et al. (mBio 9:e01003-18, 2018, screened a genome-wide CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats with Cas9) knockout library for host proteins involved in the pathogenesis of enterohemorrhagic Escherichia coli (EHEC)...
October 9, 2018: MBio
Shuning Wang, Xiaoju Li, Wangqian Zhang, Yuan Gao, Kuo Zhang, Qiang Hao, Weina Li, Zhaowei Wang, Meng Li, Wei Zhang, Yingqi Zhang, Cun Zhang
Estrogen receptor alpha (ERα), which has been detected in over 70% of breast cancer cases, is a driving factor for breast cancer growth. For investigating the underlying genes and networks regulated by ERα in breast cancer, RNA-seq was performed between ERα transgenic MDA-MB-231 cells and wild type MDA-MB-231 cells. A total of 267 differentially expressed genes (DEGs) were identified. Then bioinformatics analyses were performed to illustrate the mechanism of ERα. Besides, by comparison of RNA-seq data obtained from MDA-MB-231 cells and microarray dataset obtained from estrogen (E2) stimulated MCF-7 cells, an overlap of 126 DEGs was screened...
October 5, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Yutian Tian, Shuhan Guo, Cengceng Chen, Li Zhao, Zhen Li, Yongjian Yan
Manganese poisoning is a common occupational disease, studies have found that the susceptibility to manganese poisoning differs in individuals. We adopted genome-wide sequencing methods to screen for susceptibility genes involved in gene-mediated metabolic pathways from the perspective of manganese poisoning. We identified 18,439 genes in this study, including 14,272 known genes and 4398 new genes. We then selected 17 differential genes using p values, of which 7 genes were down-regulated and 10 genes were up-regulated...
September 29, 2018: Environmental Toxicology and Pharmacology
Pamela Y Ting, Albert E Parker, J Scott Lee, Chris Trussell, Orzala Sharif, Fabio Luna, Glenn Federe, S Whitney Barnes, John R Walker, Julie Vance, Mu-Yun Gao, Heath E Klock, Scott Clarkson, Carsten Russ, Loren J Miraglia, Michael P Cooke, Anthony E Boitano, Peter McNamara, John Lamb, Christian Schmedt, Jennifer L Snead
CRISPR-Cas9 screening allows genome-wide interrogation of gene function. Currently, to achieve the high and uniform Cas9 expression desirable for screening, one needs to engineer stable and clonal Cas9-expressing cells-an approach that is not applicable in human primary cells. Guide Swap permits genome-scale pooled CRISPR-Cas9 screening in human primary cells by exploiting the unexpected finding that editing by lentivirally delivered, targeted guide RNAs (gRNAs) occurs efficiently when Cas9 is introduced in complex with nontargeting gRNA...
October 8, 2018: Nature Methods
Hao Zeng, Bo Lu, Raffaella Zamponi, Zinger Yang, Kristie Wetzel, Joseph Loureiro, Sina Mohammadi, Martin Beibel, Sebastian Bergling, John Reece-Hoyes, Carsten Russ, Guglielmo Roma, Jan S Tchorz, Paola Capodieci, Feng Cong
Wnt/β-catenin signaling plays pivotal roles in cell proliferation and tissue homeostasis by maintaining somatic stem cell functions. The mammalian target of rapamycin (mTOR) signaling functions as an integrative rheostat that orchestrates various cellular and metabolic activities that shape tissue homeostasis. Whether these two fundamental signaling pathways couple to exert physiological functions still remains mysterious. Using a genome-wide CRISPR-Cas9 screening, we discover that mTOR complex 1 (mTORC1) signaling suppresses canonical Wnt/β-catenin signaling...
October 8, 2018: Proceedings of the National Academy of Sciences of the United States of America
Timothy P Daley, Zhixiang Lin, Xueqiu Lin, Yanxia Liu, Wing Hung Wong, Lei S Qi
Pooled CRISPR screens allow researchers to interrogate genetic causes of complex phenotypes at the genome-wide scale and promise higher specificity and sensitivity compared to competing technologies. Unfortunately, two problems exist, particularly for CRISPRi/a screens: variability in guide efficiency and large rare off-target effects. We present a method, CRISPhieRmix, that resolves these issues by using a hierarchical mixture model with a broad-tailed null distribution. We show that CRISPhieRmix allows for more accurate and powerful inferences in large-scale pooled CRISPRi/a screens...
October 8, 2018: Genome Biology
Gwen Iris L Descalsota, B P Mallikarjuna Swamy, Hein Zaw, Mary Ann Inabangan-Asilo, Amery Amparado, Ramil Mauleon, Prabhjit Chadha-Mohanty, Emily C Arocena, Chitra Raghavan, Hei Leung, Jose E Hernandez, Antonio B Lalusin, Merlyn S Mendioro, Ma Genaleen Q Diaz, Russell Reinke
The development of rice genotypes with micronutrient-dense grains and disease resistance is one of the major priorities in rice improvement programs. We conducted Genome-wide association studies (GWAS) using a Multi-parent Advanced Generation Inter-Cross (MAGIC) Plus population to identify QTLs and SNP markers that could potentially be integrated in biofortification and disease resistance breeding. We evaluated 144 MAGIC Plus lines for agronomic and biofortification traits over two locations for two seasons, while disease resistance was screened for one season in the screen house...
2018: Frontiers in Plant Science
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